Hematology Update

Hematology Department

Hospital Ampang

Case 1History

59 years old lady

No known medical illness

Presented with lower back pain for 1 month

A/W LOA and LOW

Pain worsening and bed bound

Constipation

No urinary retention

Physical Exam General : Pallor, Lethargic

Vital signs :BP : 100/70 PR : 100/min Spo2 : 99% RA

CVS /Lung /Abdomen : normal

Spine : tenderness over the lower lumbar and right paraveretebral region

Upper limbs : normal Lower limbs : tone normal

power difficulty to assessreflexes normal and plantar down going

Investigations Hb : 8.9 TWCC: 8.1 Platelet : 110

BUSE : urea : 18.3 Creat : 476 k : 3.0 Na : 135 Cl : 90

Bilirubin : 10.4 Albumin : 16 Globulin : 105

ALT : 14 ALP : 300

Ca : 3.3,Corrected Ca : 3.78

Mg : 1.0 PO4 : 1.2

Lumbosacral and pelvic X-ray : multiple lytic lesion and compression fracture over L1

U/S renal : no evidence of obstructive uropathy

Diagnosis ?

Malignant Hypercalcemia

Malignacy must be ruled out in patients that present

with a very high calcium and no other obvious cause

Malignant hypercalcemia

Occurs in about 10 to 20% of patients with cancer

- Both solid tumors and hematological malignancy

Most common: Breast, Lung, Multiple myeloma.

Signs and SymptomsInsidious symptoms and often non specific signs:

CNS : anxiety, depression, cognitive dysfunction

GIT : anorexia, constipation, abdominal pain,

pancreatitis (rare)

Renal :

-Polyuria, polydipsia (nephrogenic DI)

-Renal calculi less frequent than in Primary HyperPTH

-CKD if long standing untreated hypercalcemia

CV: Short QT interval, Supraventricular & Ventricular

arrhythmias

Treatment Intavenous hydration with isotonic saline

Volume, Volume, Volume

Up to 5l/day

Caution with elderly and heart problem

Forced Diuresis / calciuresis with frusemide

Increase renal excretion of calcium

Medical TherapyDrug Target

Organ Dose Mechanism

1)Bisphophonates Bone Palmidronate60-90mgZolendronic acid4mg

Inhibition of Osteoclast activity and differentiation

2) Steroid Bowel

Tumour (lymphoma )

Dexamethasone 4-8mg tds

Reduced absorption of calciumInhibition of ectopic production of 1,25(OH)2D3

3) Calcitonin Bone

kidney

4IU/kg SC/IM 12hourly

Inhibition of Osteoclast activityIncrease renal excretion of calcium

Administration of bisphosphonates – mainstays of Rx

Hemodialysis

- last resort, if can’t tolerate volume expansion and /or

rapid correction of hyperCa needed

Back to patient IV Drip 8 pints

IV Palmidronate 60mg given

Renal function back to normal

Ca : 2.0mmol/l

Further Ix: Multiple myeloma

Case 2 14 years old boy

No known medical illness

Presented with cough for 2 months

SOB on exertion

A/W LOA, LOW ( 6kg in 2 months)

No fever

No PTB contact, no night sweat

No hemoptysis

Other systemic review unremarkable

Physical exam Pink, Mild tachpnoea

BP : 98/50mmHg PR : 100/min

RR : 24 breathe/min Spo2 : 98% RA

Facial swollen

Dilated neck and chest wall veins

Abdomen : hepatomegaly 2cm , no splenomegaly

Upper limbs : not swollen

Investigations FBC: Hb 12.2 TWCC : 12 Platelet : 406

Renal profile : normal

Liver function test : normal

LDH : 880

Ca : 2.46

Chest X-ray

CT Thorax

Diagnosis?

Superior Vena Cava Syndrome

SVC Syndrome SVC syndrome is characterized by gradual, insidious

compression / obstruction of the superior vena cava.

Easy to compress - SVC has a thin wall & low intravascular pressure & is surrounded by rigid structures.

The low intravascular pressure also allows for the possibility of thrombus formation, such as catheter-induced thrombus.

The subsequent obstruction to flow causes an increased venous pressure, which results in interstitial edema and retrograde collateral flow.

Causes More than 90% of patients with SVC have an associated

malignancy as the cause. - Rapid growing high grade lymphoma - Primary mediastinal malignancies

(thymoma and thymic cancer, extragonadal germ-cell cancer ) - Metastatic disease to the mediastinum

Lung ca

Infectious causes (eg, syphilis, tuberculosis) have decreased because of improvements in antibiotic therapy.

Thrombosis from central venous instrumentation - Catheter, pacemaker, guidewire

Work up The diagnosis of superior vena cava syndrome (SVCS) is

often made on clinical grounds alone

Clinical presentation

-Progressive shortness of breath

-Stridor and cyanosis

-Upper body edema,

- Dilated chest wall vein

- Distended neck vein

-Distorted vision,

-Nausea, Light-headedness

Imaging

Plain radiography

Venography

CT chest

MRI

Treatment Attention to the ABCs is essential.

Supportive

- Elevate the patient’s head to decrease the hydrostatic

pressure and thereby the edema

- High dose glucocorticoid therapy

dexamethasone, 16-20 mg every 6-8h

- If cerebral/airway edema is present, consider diuretics

Endovascular shunts are increasingly used, as are thrombolytic if a thrombotic cause is present.

Definitive therapy

Urgent!!!

Obtaining a histological diagnosis before initiating treatment

Radiotherapy

Chemotherapy

- Cyclophosphamide 200mg od for 3 days

or both

Case 3 27 years old gentleman

No known medical illness

Fever for 2 weeks

Gum bleeding for 5 days

No other bleeding tendency

Mild giddiness and headache

Blurring of vision

No vomiting

No chest pain, no SOB

Physical exam Pallor, no jaundice

Tachypnoeic , gum hypertrophy

BP : 141/76mmHg

PR : 110

T: 38°C

CVS/Lung : NAD

Abdomen : hepatomegaly 3cm

Investigations Hb : 7.7 TWCC : 207 Platelet : 136

Urea : 3.6mmol/l creat :136umol/l K: 2.6mmol/l

LFT : Normal

LDH : 1376u/l

Ca: 2.09mmol/l

FBP

Diagnosis?

Hyperleukocytosis

Hyperleukocytosis and Leukostasis Define as TWC >100x109/L

Leukostasis – characterised by extremely elevated blast cell count and symptoms of decreased tissue perfusion

Presented with respiratory or neurological symptoms

Left untreated, mortality ≈ 40%

Pathophysiology Increased blood viscosity in microcirculation

Blast cell highly active and associate with release of cytokines which can exacerbate local hypoxaemia

Leukemic blast-endothelial cell interactions lead to vascular wall disruption and bleeding,

likely due to locally released cytokines such as TNF alpha, IL--1, and IL-4.

The up-regulation of adhesion receptors such as L-selectin and E-selectin which can promote adhesion to the vascular endothelium and therefore, lead to the vascular endothelium tissue invasion and poor flow through vessel

More common in AML than ALL

Myeloblast and monoblast are larger and less deformable , stickier

Signs and symptoms Respiratory distress, hypoxemia, diffuse interstitial or

alveolar infiltrates.

CNS

- Confusion, somnolence, stupor, delirium, coma

- Headache, dizziness, weakness, gait

- Papilledema, retinal vein distention, retinal

hemorrhages

Coagulopathy/ DIC

Renal Failure

Lab tests Cytopenia

Increased PT/ PTT

Hyperuricemia

Hyperphosphatemia

Hypocalcemia

Hyperkalemia

Increased Lactate-- evidence for poor tissue perfusion

Treatment Avoidance of transfusion of red blood cells when

possible.

Careful correction of coagulopathy with FFP and Platelets

Hydration and avoid K supplement

Prevention of Tumor Lysis

Allopurinol/ Rasburicase

Cytoreduction

Initiation of Induction Chemotherapy

Hydroxyurea - 50 - 100mg/kg/day PO 12hrs

Cytarabine ( Ara C ) – 100mg/m2 or 200mg od

for 3 days

Cyclophosphamide – 200mg/m2 or 200mg od

for 3 days

Steroid

Leukopheresis – CVS, Neurological , Prapism

Case 4 24 yo Malay female

Diagnosed hodgkin lymphoma in 2012

Opt for alternative treatment

Become quadriplegic since the past 1/52.

Initially started with numbness then unable to move both upper limb and lower limb.

No hx of trauma

BO –normal

Difficulty passing urine

Physical exam Vital signs stable

Febrile

Bulky right neck swelling and bilateral axillary nodes palpable

NeurologicalPower bilateral UL and LL --> 0/5Sensation intactTone reduced

Diagnosis?

Next Step?

Spinal Cord Compression

Imaging Urgent Imaging

No excuse for delay

MRI

CT scan myelography

X-ray- limited sensitivity and specificity

Spinal Cord Compression Prompt diagnosis and management to prevent

irreversible damage and paralysis

Causes

- Hematology – Multiple myeloma ( plasmacytoma ),

lymphoma

- Solid tumours – Breast, Lung, Prostate

- Trauma, infection and etc

Up to 7% patients with malignancy disease

Signs and Symptoms Depend on the site, extent and rate of development of

the lesion

Back pain – 90%

Sensory disturbance or loss – sensory level

Reduction of power in the limbs

Difficulty walking

Sphincter disturbance

Treatment High dose steroid

- 16-20mg 4-6hourly

Referral – Orthopaedic team

- Instability

- Spinal shock

- Diagnosis

Radiotherapy

Chemotherapy

References Hematological Emergencies

Medicine, Volume 41, Issue 5, May 2013, Pages 306-311

Oncologic Emergencies

Intensive Care of the Cancer Patient

Volume 26, Issue 1, January 2010, Pages 181–205

Hematological Emergencies

Annals of Oncology 18 (Supplement 1): i45–i48, 2007

Oncologic Emergencies: Diagnosis and Treatment

Mayo Clinic Proceedings, Volume 81, Issue 6, June 2006, Pages 835-848

A 2011 Updated Systematic Review and Clinical Practice Guideline for the

Management of Malignant Extradural Spinal Cord Compression

International Journal of Radiation Oncology*Biology*Physics, Volume 84,

Issue 2, 1 October 2012, Pages 312-317